Previous work has shown that CDC27 acts late in G2 of the cell cycle, after DNA replication but prior to the onset of chromosome segregation and that the encoded protein binds to the mitotic spindle. Several unsuccessful attempts were made to clone the human homolog by conventional techniques. A search of dbEST (see report number Z01-LM-00015-01-BRB) showed a weak but significant match to a human brain protein. Additional sequencing confirmed the homology and the DNA was mapped to human chromosome 17q21-24 thus becoming a candidate gene for human breast cancer susceptibility. A computer study was performed using a training set of known yeast-human homolog pairs to assess the general utility of this method of gene discovery and to optimize search parameters. Over the next three years we will systematically search for new yeast-human homolog pairs and map approximately 1000 of these to human chromosomes. We expect to find a number of yeast proteins that will become candidates for human disease genes by virtue of their map locations.